title: Vardenafil improves penile erection in type 2 diabetes mellitus patients with erectile dysfunction: role of tropomyosin.
abstract: BACKGROUND
  Evidences have been suggested that phosphodiesterase type 5 (PDE5) inhibition promotes vasculoprotective benefits in patients with cardiovascular diseases.
  
  
  OBJECTIVE
  The aim of this study is to analyze the systemic effect of PDE5 inhibition in type 2 diabetes mellitus patients with erectile dysfunction (ED) determining changes in the expression levels of plasma proteins.
  
  
  METHODS
  Seventeen patients with controlled type 2 diabetes mellitus and ED were included in the study. Patients received vardenafil hydrochloride 20 mg on demand during 12 weeks. At the beginning and 12 weeks after vardenafil administration, plasma samples were collected and analyzed using proteomics.
  
  
  METHODS
  International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) and plasma protein expression before and after vardenafil administration. Nitrate/nitrite release, PDE5, and soluble guanylate cyclase (sGC) expression and cyclic guanosine monophosphate (cGMP) content in cultured bovine aortic endothelial cells (BAECs).
  
  
  RESULTS
  The IIEF-EFD score was markedly improved after 12 weeks of vardenafil administration. Plasma levels of alpha 1-antitrypsin isotypes 4 and 6 and β-tropomyosin were decreased, whereas apolipoprotein AI isoype 5 was increased 12 weeks after vardenafil administration. Only β-tropomyosin plasma levels were inversely correlated with IIEF-EFD score. Tropomyosin has been added to cultured BAECs and after 24 hours reduced the protein expression level of sGC-β1 subunit and decreased the cGMP content. Tropomyosin did not modify PDE5 expression and nitric oxide release in BAECs as compared with control BAECs. Vardenafil (10 μg/mL) did not modify sGC-β1 subunit expression in tropomyosin + vardenafil-incubated BAECs; however, vardenafil significantly reversed the reduction of cGMP content induced by tropomyosin.
  
  
  CONCLUSIONS
  Vardenafil administration improved erectile functionality in controlled type 2 diabetes mellitus patients with ED, which was associated with reduction of circulating plasma β-tropomyosin levels. Tropomyosin affected by itself the cGMP generating system suggesting a possible new mechanism involved in ED. Vardenafil reversed the reduction effect of cGMP content elicited by tropomyosin in BAECs.
authors.affiliation: Cardiovascular Research Unit, Cardiology Department of Hospital Clínico San Carlos de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Zamorano-León
authors.forename: Carlos
authors.initials: C
authors.lastname: Olivier
authors.forename: Natalia
authors.initials: N
authors.lastname: de Las Heras
authors.forename: Petra J
authors.initials: PJ
authors.lastname: Mateos-Cáceres
authors.forename: Ricardo
authors.initials: R
authors.lastname: Brime Menéndez
authors.forename: Pablo
authors.initials: P
authors.lastname: Rodríguez-Sierra
authors.forename: Naihara
authors.initials: N
authors.lastname: Martín Palacios
authors.forename: Luis San José
authors.initials: LS
authors.lastname: Manso
authors.forename: Javier
authors.initials: J
authors.lastname: Modrego
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: López-Farré
mesh_terms: D000818:Animals; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D007172:Erectile Dysfunction / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D010410:Penile Erection / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use; D014335:Tropomyosin / Q000097:blood / Q000502:physiology*; D000069058:Vardenafil Dihydrochloride
chemical_list: D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D018160:Receptors, Cytoplasmic and Nuclear; D013450:Sulfones; D014227:Triazines; D014335:Tropomyosin; D009569:Nitric Oxide; D000069058:Vardenafil Dihydrochloride; D010727:Phosphoric Diester Hydrolases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP
keywords: Diabetes Mellitus; Erectile Dysfunction; PDE5 Inhibitors; Proteomics; Vardenafil